Studies on the Mechanism of Suppression of the Immune Response by Synthetic, Non-Toxic Adjuvants

摘要

The immunomodulatory action of a non-toxic monophosphoryl lipid A (MPL) and a toxic diphosphoryl lipid A (DPL) fraction derived from endotoxins of the heptoseless mutants of bacteria were compared. Both derivatives retained the ability characteristic of lipopolysaccharides, to enhance antibody formation in young adult mice when injected along with antigen and suppress antibody production when given a day before antigen. In aging mice, a model of immunodeficiency, a marked restoration of antibody formation was observed when antigen was injected together with either MPL or DPL. Levels of antibody in these aging mice were comparable to those observed in young adult mice. Moreover, both MPL and DPL enhanced antibody production significantly in the endotoxin low-responder mouse strains, C3H/HeJ and C57Bl/10 ScN, whereas, phenol-water extracted endotoxin from an R-7 mutant was ineffective. MPL and DPL also acted as suppressive agents when administered prior to antigen in the C3H/HeJ strain. Thus, the results from these studies show that (a) the toxic properties of lipid A can be removed without eliminating immunomodulating activity, and (b) such lipidic compounds can overcome the immunologic lesions of immunodeficient and hyporesponsive animals. Originator supplied keywords include: Polyribonucleotides, and Muramyl dipeptides.